9TDA
ERAP1 in complex with 1-[2-(5-bromo-7-fluoro-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)acetamido]-4,4-difluorocyclohexane-1-carboxylic acid
This is a non-PDB format compatible entry.
Summary for 9TDA
| Entry DOI | 10.2210/pdb9tda/pdb |
| Descriptor | Endoplasmic reticulum aminopeptidase 1, ZINC ION, SUCCINIC ACID, ... (7 entities in total) |
| Functional Keywords | erap1, peptide binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 106675.75 |
| Authors | |
| Primary citation | Law, R.P.,Wall, I.D.,Lonsdale, R.,Hryczanek, R.P.,Barker, D.,Barrett, T.N.,Bit, R.A.,Coward, J.J.,Gray, M.W.,Green, D.V.S.,Hall, C.J.,Hancock, A.P.,Haslam, C.,Hirst, D.J.,Hryczanek, H.F.,Hutchinson, J.P.,Kitchen, S.,Marcus, D.,Marklew, J.,Mason, J.,Measom, N.D.,Neu, M.,Peace, S.,Phillipou, A.,Pickett, S.D.,Pogany, P.,Rowedder, J.,Rowland, P.,Scott-Stevens, P.,Seal, G.A.L.,Sheehan, H.,Stratikos, E.,Tayler, C.,Taylor, J.A.,Tinworth, C.P.,Vitulli, G. Automated Molecular Design in BRADSHAW, Applied to the Optimization of ERAP1 Inhibitors. J.Med.Chem., 69:8869-8896, 2026 Cited by PubMed Abstract: Generative design and machine learning are increasingly prevalent in medicinal chemistry. To pilot the comprehensive use of automated molecular design on a project, the BRADSHAW platform was used to optimize a series of inhibitors of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), an emerging target in cancer immunotherapy and autoimmune diseases. Through four consecutive iterations applying in silico molecular generation, property prediction and filtering, we conducted a multiparameter optimization of potency, physicochemical properties and pharmacokinetics. Continuous refinement of Machine Learning (ML) models led to improved scoring accuracy and compound quality, culminating in identification of in vitro and in vivo tool molecules. We also discuss our reflections on the pilot and integration of automated design into medicinal chemistry projects, including observations of the human factors resulting from increased use of computational design, and recommendations for future projects. PubMed: 41973545DOI: 10.1021/acs.jmedchem.5c03071 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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